2A6D: Crystal structure analysis of the anti-arsonate germline antibody 36-65 in complex with a phage display derived dodecapeptide RLLIADPPSPRE

Correlation between the promiscuity of the primary antibody response and conformational flexibility in a germline antibody was addressed by using germline antibody 36-65. Crystallographic analyses of the 36-65 Fab with three independent dodecapeptides provided mechanistic insights into the generation of antibody diversity. While four antigen-free Fab molecules provided a quantitative description of the conformational repertoire of the antibody CDRs, three Fab molecules bound to structurally diverse peptide epitopes exhibited a common paratope conformation. Each peptide revealed spatially different footprints within the antigen-combining site. However, a conformation-specific lock involving two shared residues, which were also associated with hapten binding, was discernible. Unlike the hapten, the peptides interacted with residues that undergo somatic mutations, suggesting a possible mechanism for excluding "nonspecific" antigens during affinity maturation. The observed multiple binding modes of diverse epitopes within a common paratope conformation of a germline antibody reveal a simple, yet elegant, mechanism for expanding the primary antibody repertoire.
PDB ID: 2A6DDownload
MMDB ID: 39555
PDB Deposition Date: 2005/7/2
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 2A6D: dimeric; determined by author and by software (PISA)
Molecular Components in 2A6D
Label Count Molecule
Proteins (2 molecules)
Germline Antibody 36-65 FAB Light Chain
Molecule annotation
Germline Antibody 36-65 FAB Heavy Chain
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB